IMMUNE RESPONSE TO POLYSACCHARIDE ANTIGENS

对多糖抗原的免疫反应

• 批准号: 2057459
• 负责人: ELISABETH Elaine ADDERSON
• 金额: $ 8.26万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2057459
• 关键词: Haemophilus influenzae; Neisseria meningitidis; antibacterial antibody; antibody formation; antibody specificity; bacterial polysaccharides; biological models; chimeric proteins; gene rearrangement; genetically modified animals; human genetic material tag; human tissue; immunoglobulin genes; immunoglobulin structure; laboratory mouse; laboratory rat; microorganism immunology; model design /development; molecular cloning; transfection

Polysaccharide-encapsulated bacteria cause substantial morbidity and mortality in young infants and other "high risk" groups. Antibody directed against capsular polysaccharide protects against these infections. Unfortunately, children less that two years of age, for unknown reasons, respond poorly to polysaccharide vaccines. Conjugation of bacterial polysaccharides to protein carriers improves the immunogenicity of these antigens, however different protein carriers elicit varying serum antibody concentrations and antibody of different functional activity. Furthermore, a large number of encapsulated bacteria cause human disease and individual vaccines must be developed for each. The aim of this project is to a) determine the relationship between antibody structure and functional activity and b) understand the molecular basis of the age-dependent - unresponsiveness to polysaccharide antigens. These findings will be invaluable in the design and assessment of vaccines directed against important bacterial pathogens. This is a five year project directed at the understanding of the role of important immunoglobulin variable region genes in determining fine antigen specificity and functional activity of anti-bacterial antibodies and the regulation of expression of these antibodies in early life. Specific aims include: (1) the determination of immunoglobulin structural components most important in defining fine antigen specificity of anti-bacterial polysaccharide antibodies, (2) definition of the role of heavy chain isotype and important immunoglobulin variable region genes in the functional activity of these antibodies, (3) determination of the ability of anti-polysaccharide antibody heavy chain/"surrogate" light chain complexes to bind antigen and, thus, influence the early antibody repertoire, and (4) the development of a transgenic mouse model in order to study the regulation of anti-polysaccharide antibodies in early development.

多糖封装的细菌会导致大量发病率和 年轻婴儿和其他“高风险”群体的死亡率。抗体定向 针对囊囊多糖可预防这些感染。 不幸的是，由于未知原因，儿童少于两岁， 对多糖疫苗的反应不佳。细菌的结合 蛋白质载体的多糖改善了这些载体的免疫原性 抗原，但是不同的蛋白质载体会引起不同的血清抗体 不同功能活性的浓度和抗体。此外， 大量封装细菌引起人类疾病和个体 必须为每种疫苗开发疫苗。该项目的目的是a） 确定抗体结构与功能之间的关系 活性和b）了解年龄依赖性的分子基础 - 对多糖抗原的反应无反应。这些发现将是 针对针对的疫苗的设计和评估无价 重要的细菌病原体。 这是一个针对理解角色的五年项目 重要的免疫球蛋白可变区域基因确定细抗原 抗细菌抗体的特异性和功能活性和 调节这些抗体在早期的表达。具体目标 包括：（1）确定免疫球蛋白结构成分 在定义抗细菌的细胞特异性方面最重要的 多糖抗体，（2）重链作用的定义 同种型和重要的免疫球蛋白可变区域基因 这些抗体的功能活性，（3）确定能力 抗可糖浆抗体重链/“替代”轻链 复合物结合抗原，从而影响早期抗体 曲目和（4）开发转基因小鼠模型按顺序开发 研究早期的抗抗糖糖抗体的调节 发展。